Commentary

Few well designed studies have assessed treatments for MDD in adolescents. A recent public health advisory from the US Food
and Drug Administration (FDA)1 questioned the safety of SSRIs because of increased suicidal behaviours in adolescents and children.2 In the UK, the regulator has strongly advised against the use of all SSRIs except fluoxetine in adolescents and children
(http://www.mhra.gov.uk/news/ssri_101203.htm accessed 13 Jan 2005).

TADS offers some strong support for 12 weeks of fluoxetine plus ⩾11 sessions of simultaneous CBT. Study strengths are the
RCT design, double blinding in the fluoxetine and placebo groups, the inclusion of adolescents with comorbidities, and the
data safety and monitoring protocol conducted by the National Institute of Mental Health.

Patients in the CBT plus fluoxetine and CBT alone groups were not blinded, which might have affected the findings if these
patients expected improved outcomes. Adolescents with substance abuse, recent suicide attempts, or suicidal ideation were
excluded; thus findings are not generalisable to all adolescents with MDD. Some of these adolescents are most in need of treatment.
A study weakness was the exclusion of non-English speaking adolescents or parents. The modal income reflected a high middle
class, thus missing many adolescents with lower socioeconomic status who have MDD. The study report did not describe how the
fidelity of the CBT intervention was monitored. The treatment duration of 12 weeks does not offer support for longer use of
either treatment.

TADS provides evidence that fluoxetine plus CBT is effective for adolescents with MDD, including those with some comorbid
conditions. However, the advisory from the FDA should also be considered. Antidepressant medications may increase the risk
of suicidality or other harm related adverse events. Nurses must continue to monitor depressed adolescents for suicidal thinking
and behaviour. This includes providing anticipatory guidance to parents or guardians about signs to observe and actions to
take. Further study is needed to determine the longer term effects of combined pharmacological and psychotherapeutic treatments
for the wide array of adolescents who have MDD.